Pathway to global elimination of hepatitis B: HBV cure is just the first step.

Hepatitis B (HBV) is a major cause of global morbidity and mortality, and the leading cause of liver cancer worldwide. Significant advances have recently been made toward the development of a finite HBV treatment that achieves permanent loss of HBsAg and HBV DNA (so-called "HBV cure"), which could provide the means to eliminate HBV as a public health threat. However, the HBV cure is just one step toward achieving WHO HBV elimination targets by 2030, and much work must be done now to prepare for the successful implementation of the HBV cure. In this review, we describe the required steps to rapidly scale-up future HBV cure equitably. We present key actions required for successful HBV cure implementation, integrated within the World Health Organization (WHO) Global Health Sector Strategy (GHSS) 2022-2030 framework. Finally, we highlight what can be done now to progress toward the 2030 HBV elimination targets using available tools to ensure that we are preparing, but not waiting, for the cure.

Strategies for Removal of Barriers to Hepatitis C Elimination in Sub-Saharan Africa.

Hepatitis C virus (HCV) infection is a major global health threat, with serious consequences including liver cirrhosis and cancer. Despite efforts to combat HCV, an estimated 1.5 million new infections occur each year and HCV was the sixth leading cause of death in 2017. Nevertheless, political leaders are increasingly interested in the fight against HCV, and the achievements of countries such as Rwanda, Egypt, India, Mongolia, Pakistan, Georgia, and Ukraine have given hope that the elimination plan to reduce new infections to 90% and mortality to 65% by 2030 is possible. It is true that some African countries can attest to the difficulty of operationalizing the HCV program with expensive testing platforms and HCV drugs that few could afford in the past, let alone the logistics involved, given that active case detection is an asset for HCV elimination. The inability to add direct-acting antivirals (DAAs) to the national essential drug list and negotiate DAA cost subsidies remains a major challenge in Africa. The lessons learned from implementing and scaling up the human immunodeficiency virus program can provide a strong framework to deliver comprehensive HCV services. We present the strategies used by some African countries to move toward HCV elimination, describe the challenges they have faced, and suggest realistic solutions.

Global burden of primary liver cancer in 2020 and predictions to 2040.

BACKGROUND & AIMS: The burden of liver cancer varies across the world. Herein, we present updated estimates of the current global burden of liver cancer (incidence and mortality) and provide predictions of the number of cases/deaths to 2040. METHODS: We extracted data on primary liver cancer cases and deaths from the GLOBOCAN 2020 database, which includes 185 countries. Age-standardised incidence and mortality rates (ASRs) per 100,000 person-years were calculated. Cases and deaths up to the year 2040 were predicted based on incidence and mortality rates for 2020 and global demographic projections to 2040. RESULTS: In 2020, an estimated 905,700 people were diagnosed with, and 830,200 people died from, liver cancer globally. Global ASRs for liver cancer were 9.5 and 8.7 for new cases and deaths, respectively, per 100,000 people and were highest in Eastern Asia (17.8 new cases, 16.1 deaths), Northern Africa (15.2 new cases, 14.5 deaths), and South-Eastern Asia (13.7 new cases, 13.2 deaths). Liver cancer was among the top three causes of cancer death in 46 countries and was among the top five causes of cancer death in 90 countries. ASRs of both incidence and mortality were higher among males than females in all world regions (male:female ASR ratio ranged between 1.2-3.6). The number of new cases of liver cancer per year is predicted to increase by 55.0% between 2020 and 2040, with a possible 1.4 million people diagnosed in 2040. A predicted 1.3 million people could die from liver cancer in 2040 (56.4% more than in 2020). CONCLUSIONS: Liver cancer is a major cause of death in many countries, and the number of people diagnosed with liver cancer is predicted to rise. Efforts to reduce the incidence of preventable liver cancer should be prioritised. LAY SUMMARY: The burden of liver cancer varies across the world. Liver cancer was among the top three causes of cancer death in 46 countries and was among the top five causes of cancer death in 90 countries worldwide. We predict the number of cases and deaths will rise over the next 20 years as the world population grows. Primary liver cancer due to some causes is preventable if control efforts are prioritised and the predicted rise in cases may increase the need for resources to manage care of patients with liver cancer.

Progress Toward the Elimination of Mother-to-Child Transmission of Hepatitis B Virus - Worldwide, 2016-2021.

Mother-to-child transmission (MTCT) of hepatitis B virus (HBV) often results in chronic HBV infection, the leading cause of cirrhosis and liver cancer (1). If not vaccinated, nine in 10 children infected at birth will become chronically infected. Globally, an estimated 6.4 million (range = 4.4-10.8 million) children aged ≤5 years are living with chronic HBV infection (2). In 2016, the World Health Assembly endorsed the goal to eliminate viral hepatitis as a public health threat by 2030, including the elimination of MTCT of HBV (3). Elimination of MTCT of HBV can be validated by demonstrating ≤0.1% prevalence of HBV surface antigen (HBsAg) among children aged ≤5 years, as well as ≥90% coverage with hepatitis B birth dose (HepB-BD) and 3 doses of hepatitis B vaccine (HepB3) (4,5). This report describes global progress toward elimination of MTCT of HBV during 2016-2021. By December 2020, 190 (98%) of 194 World Health Organization (WHO) member states* had introduced universal infant vaccination with hepatitis B vaccine (HepB), and 110 (57%) countries provided HepB-BD to all newborns. During 2016-2020, global HepB3 coverage remained between 82% and 85%, whereas HepB-BD coverage increased from 37% to 43%. In 2020, among the 99 countries reporting both HepB3 and HepB-BD coverage, 41 (41%) achieved ≥90% coverage with both. By December 2021, serosurveys documented ≤0.1% HBsAg prevalence among children in 11 countries. Accelerating HepB-BD introduction, increasing HepB3 coverage, and monitoring programmatic and impact indicators are essential for elimination of MTCT of HBV.

Eliminating mother-to-child transmission of human immunodeficiency virus, syphilis and hepatitis B in sub-Saharan Africa.

Triple elimination is an initiative supporting the elimination of mother-to-child transmission of three diseases - human immunodeficiency virus (HIV) infection, syphilis and hepatitis B. Significant progress towards triple elimination has been made in some regions, but progress has been slow in sub-Saharan Africa, the region with the highest burden of these diseases. The shared features of the three diseases, including their epidemiology, disease interactions and core interventions for tackling them, enable an integrated health-systems approach for elimination of mother-to-child transmission. Current barriers to triple elimination in sub-Saharan Africa include a lack of policies, strategies and resources to support the uptake of well established preventive and treatment interventions. While much can be achieved with existing tools, the development of new products and models of care, as well as a prioritized research agenda, are needed to accelerate progress on triple elimination in sub-Saharan Africa. In this paper we aim to show that health systems working together with communities in sub-Saharan Africa could deliver rapid and sustainable results towards the elimination of mother-to-child transmission of all three diseases. However, stronger political support, expansion of evidence-based interventions and better use of funding streams are needed to improve efficiency and build on the successes in prevention of mother-to-child transmission of HIV. Triple elimination is a strategic opportunity to reduce the morbidity and mortality from HIV infection, syphilis and hepatitis B for mothers and their infants within the context of universal health coverage.

La triple élimination est une initiative visant à soutenir l'éradication de la transmission mère-enfant de trois maladies ­ l'infection au virus de l'immunodéficience humaine (VIH), la syphilis et l'hépatite B. Bien que des avancées considérables aient été observées en ce sens dans certaines régions, les progrès demeurent lents en Afrique subsaharienne, pourtant durement touchée par ces maladies. Les caractéristiques communes aux trois affections, notamment leur épidémiologie, les interactions entre elles et les principales interventions nécessaires à leur prise en charge permettent aux systèmes de santé d'adopter une approche intégrée pour éviter la transmission mère-enfant. Plusieurs obstacles entravent actuellement la triple élimination en Afrique subsaharienne, parmi lesquels l'absence de politiques, de stratégies et de ressources pour garantir la disponibilité de traitements préventifs et curatifs bien établis. Les outils existants offrent déjà de nombreuses solutions; mais pour accélérer la progression de cette triple élimination en Afrique subsaharienne, il est indispensable de développer de nouveaux produits et modèles de soins, ainsi qu'un programme de recherche prioritaire. Dans le présent document, nous voulons montrer que si les systèmes de santé collaborent avec les communautés en Afrique subsaharienne, ils pourront obtenir des résultats rapides et durables en vue d'éradiquer la transmission mère-enfant des trois maladies susmentionnées. Néanmoins, une telle démarche implique un soutien politique massif, l'expansion des interventions fondées sur des données scientifiques, et une meilleure utilisation des sources de financement afin d'améliorer l'efficacité et de s'appuyer sur les réussites en matière de prévention de la transmission du VIH de la mère à l'enfant. La triple élimination représente une occasion stratégique de réduire la morbidité et la mortalité liées à l'infection au VIH, à la syphilis et à l'hépatite B, tant chez les mères que chez les nourrissons, dans un contexte de couverture maladie universelle.

La triple eliminación es una iniciativa que apoya la eliminación de la transmisión maternoinfantil de tres enfermedades: la infección por el virus de la inmunodeficiencia humana (VIH), la sífilis y la hepatitis B. En algunas regiones se han logrado avances significativos hacia la triple eliminación, pero los progresos se han desarrollado con mayor lentitud en el África subsahariana, la región con la mayor carga de estas enfermedades. Las características comunes de las tres enfermedades, como su epidemiología, las interacciones entre ellas y las intervenciones básicas para combatirlas, permiten un enfoque integrado de los sistemas de salud para la eliminación de la transmisión maternoinfantil. Los obstáculos actuales para la triple eliminación en el África subsahariana incluyen la falta de políticas, estrategias y recursos para apoyar la adopción de intervenciones preventivas y de tratamiento bien establecidas. Aunque se puede lograr mucho con las herramientas existentes, se necesita el desarrollo de nuevos productos y modelos de atención, así como una agenda de investigación prioritaria, para acelerar el progreso de la triple eliminación en el África subsahariana. En este documento pretendemos demostrar que los sistemas de salud que trabajan conjuntamente con las comunidades del África subsahariana podrían obtener resultados rápidos y sostenibles hacia la eliminación de la transmisión maternoinfantil de las tres enfermedades. Sin embargo, se necesita un mayor apoyo político, la ampliación de las intervenciones basadas en la evidencia y un mejor uso de los flujos de financiación para mejorar la eficiencia y aprovechar los éxitos en la prevención de la transmisión maternoinfantil del VIH. La triple eliminación es una oportunidad estratégica para reducir la morbilidad y la mortalidad de la infección por el VIH, la sífilis y la hepatitis B para las madres y sus hijos en el contexto de la cobertura sanitaria universal.

Innovative strategies for the elimination of viral hepatitis at a national level: A country case series.

Viral hepatitis is a leading cause of morbidity and mortality worldwide, but has long been neglected by national and international policymakers. Recent modelling studies suggest that investing in the global elimination of viral hepatitis is feasible and cost-effective. In 2016, all 194 member states of the World Health Organization endorsed the goal to eliminate viral hepatitis as a public health threat by 2030, but complex systemic and social realities hamper implementation efforts. This paper presents eight case studies from a diverse range of countries that have invested in responses to viral hepatitis and adopted innovative approaches to tackle their respective epidemics. Based on an investment framework developed to build a global investment case for the elimination of viral hepatitis by 2030, national activities and key enablers are highlighted that showcase the feasibility and impact of concerted hepatitis responses across a range of settings, with different levels of available resources and infrastructural development. These case studies demonstrate the utility of taking a multipronged, public health approach to: (a) evidence-gathering and planning; (b) implementation; and (c) integration of viral hepatitis services into the Agenda for Sustainable Development. They provide models for planning, investment and implementation strategies for other countries facing similar challenges and resource constraints.

Osteopontin and latent-TGF ß binding-protein 2 as potential diagnostic markers for HBV-related hepatocellular carcinoma.

Chronic Hepatitis B (HB) is the main risk factor for chronic liver disease (CLD) and hepatocellular carcinoma (HCC) in many low-resource countries, where diagnosis is constrained by lack of clinical, histopathological and biomarker resources. We have used proteomics to detect plasma biomarkers that outperform α-Fetoprotein (AFP), the most widely used biomarker for HCC diagnosis in low-resource contexts. Deep-plasma proteome analysis was performed in HCC patients, patients with CLD and in HB-carrier controls from Thailand (South-East Asia) and The Gambia (West-Africa). Mass spectrometry profiling identified latent-transforming growth factor ß binding-protein 2 (LTBP2) and Osteopontin (OPN) as being significantly elevated in HCC versus CLD and controls. These two proteins were further analyzed by ELISA in a total of 684 plasma samples, including 183 HCC, 274 CLD and 227 asymptomatic controls. When combined, LTBP2 and OPN showed an area under the receiver operating curve of 0.85 in distinguishing HCC from CLD in subjects with AFP <20 ng/mL. In a prospective cohort of 115 CLD patients from Korea, increased plasma levels of LTBP2 and/or OPN were detected in plasma collected over 2 years prior to diagnosis in 21 subjects who developed HCC. Thus, the combination of LTBP2 and OPN outperformed AFP for diagnosis and prediction of HCC and may therefore improve biomarker-based detection of HBV-related HCC.

Progress towards elimination of viral hepatitis: a Lancet Gastroenterology & Hepatology Commission update.

The top 20 highest burdened countries (in disability-adjusted life years) account for more than 75% of the global burden of viral hepatitis. An effective response in these 20 countries is crucial if global elimination targets are to be achieved. In this update of the Lancet Gastroenterology & Hepatology Commission on accelerating the elimination of viral hepatitis, we convene national experts from each of the top 20 highest burdened countries to provide an update on progress. Although the global burden of diseases is falling, progress towards elimination varies greatly by country. By use of a hepatitis elimination policy index conceived as part of the 2019 Commission, we measure countries' progress towards elimination. Progress in elimination policy has been made in 14 of 20 countries with the highest burden since 2018, with the most substantial gains observed in Bangladesh, India, Indonesia, Japan, and Russia. Most improvements are attributable to the publication of formalised national action plans for the elimination of viral hepatitis, provision of publicly funded screening programmes, and government subsidisation of antiviral treatments. Key themes that emerged from discussion between national commissioners from the highest burdened countries build on the original recommendations to accelerate the global elimination of viral hepatitis. These themes include the need for simplified models of care, improved access to appropriate diagnostics, financing initiatives, and rapid implementation of lessons from the COVID-19 pandemic.

Gastrointestinal Bleeding in Children: The Role of Endoscopy and the Sheffield Scoring System in a Resource-Limited Setting.

Objective: To document the clinical presentation, endoscopic diagnosis, and Sheffield scores of children with gastrointestinal (GI) bleeding who were referred for endoscopy at the Lagos University Teaching Hospital. The participants who needed endoscopy based on clinical criteria and according to the Sheffield scores were also documented. Methods: This study analyzed the records of 111 children with GI bleeding retrospectively from January 2013 to January 2021, while 9 children were recruited prospectively from February 2021 to March 2022. Receiver operating curves and area under the curve were generated to test the ability of the Sheffield scores to predict rebleeds, mortality, and the need for endoscopic intervention for upper GI bleeds. Results: One hundred and twenty participants were recruited. Ninety-one (75.8%) presented with upper GI bleeding (UGIB), while 29 (24.2%) had lower GI bleeding (LGIB). Only 70 (58.3%) (53 UGIB and 17 LGIB) had endoscopy performed. For UGIB, 5 (9.4%) had no source of the bleeding identified at endoscopy, 12 (22.6%) had variceal bleeding, and 36 (67.9%) had nonvariceal bleeding. Colonoscopy revealed juvenile polyps in 5 (29.4%), indeterminate colitis in 5 (29.4%), ulcerative colitis in 4 (23.5%), Crohn's disease in 1 (5.9%), and hemorrhoids in 2 (11.8%) participants, respectively. The Sheffield score was ≥8 in 42 (46.1%) of the participants who presented only with UGIB (hematemesis and melena). The scores were significantly related to the type of bleeds, rebleeds, and deaths (P = 0.00). Conclusion: The clinical and endoscopic findings in this study are similar to those reported previously. The Sheffield scoring was useful in assessing Nigerian children. However, due to limited access and other restraints, endoscopy was not performed on all the study participants even when the scoring system was suggestive. The availability, and therefore, utility of GI endoscopy in this setting are still suboptimal. The need for the provision of adequate equipment and resources and the training of personnel is thus recommended.

Appropriateness and diagnostic yield of open access gastroscopy in two tertiary centers in South-western Nigeria.

Background: There is need for the appropriate use of gastroscopy. Objective: To determine the appropriateness of upper gastrointestinal endoscopy, and its association with significant endoscopy findings in our environment. Methods: This was a prospective study of subjects who underwent gastroscopy at two centers in south-western Nigeria between August 2020 and August 2021. Indications were classified as either appropriate or inappropriate according to the ASGE guidelines, gastroscopic findings as either significant or not significant, patients as either elderly (≥ 60 years) or not, inpatients or outpatients, and referrals as either gastroenterologist referral, or not. Results: There were 227 subjects, 131 (57.7%) females, mean age 45 ± 13.7 years. Fifteen percent were elderly, 65.6% were gastroenterologist referrals, 14.1% were inpatients, while 45.8% had co-morbidities. Endoscopy was appropriately indicated in 81.9%, and significant endoscopy findings were detected in 95.6%. Appropriateness was not associated with significant endoscopy findings. The sensitivity, specificity and AUROC of the ASGE guidelines were 10%, 82%, and 0.46 respectively. Conclusion: According to our study, most procedures are appropriately indicated. However, appropriateness did not determine endoscopy yield. Larger studies are needed to determine the utility of the ASGE guidelines in our environment.

Hepatocellular carcinoma presentation and prognosis among Nigerian adults with and without HIV.

INTRODUCTION: Hepatocellular carcinoma (HCC) is an increasing cause of mortality in Nigeria among persons with HIV (PLH), as access to antiretroviral therapy (ART) improves. In this study we describe clinical, radiological, and laboratory characteristics in Nigerian adults with HCC, with and without HIV, and examine how HIV impacts survival. METHODS: This prospective observational study was conducted between August 2018 and November 2021 at two Nigerian hospitals [Jos University Teaching Hospital (JUTH) and Lagos University Teaching Hospital (LUTH)]. Subjects ≥18 years with HCC diagnosed according to American Association for the Study of Liver Diseases (AASLD) criteria were included. Baseline characteristics were compared, and Kaplan-Meier curves were generated to estimate survival. RESULTS: 213 subjects [177 (83%) without HIV and 36 (17%) with HIV (PLH)] were enrolled. Median age was 52 years (IQR 42,60) and most subjects were male (71%). 83% PLH were on antiretroviral therapy (ART). Hepatitis B surface antigen (HBsAg) positivity was similar between the two groups [91/177 (51%) without HIV vs. 18/36 (50%) with HIV; p = 0.86]. 46/213 (22%) subjects had active hepatitis C (anti-HCV+/HCV RNA>10 IU/mL). Cirrhosis was more common in PLH but there were no other significant differences in clinical and tumor characteristics between the groups. Overall, 99% subjects were symptomatic and 78% in late-stage HCC. Median overall survival was significantly shorter in PLH vs. without HIV (0.98 months vs 3.02 months, HR = 1.55, 95%CI 1.02, 2.37, p = 0.04). This association was not significant after adjusting for known risk factors including gender, current alcohol use, alpha-fetoprotein (AFP), albumin, and total bilirubin (HR = 1.38, 95%CI 0.84, 2.29, p = 0.21). CONCLUSION: HCC presented late with an extremely poor overall prognosis, highlighting the urgent need for more intensive surveillance in Nigeria to diagnose HCC at earlier stages. Early diagnosis and management of viral hepatitis, and access to HCC therapies, could prevent early mortality among persons with HCC, especially among PLH.

TP53 R249S mutation, genetic variations in HBX and risk of hepatocellular carcinoma in The Gambia.

In regions with high prevalence of chronic hepatitis B virus (HBV) infection and dietary aflatoxin B(1) (AFB(1)) exposure, hepatocellular carcinomas (HCCs) often contain TP53 mutation at codon 249 (R249S). Furthermore, a C-terminal truncated HBx protein expressed from hepatocyte integrated HBV is associated with HCC development. This study evaluates the association between R249S and HBX status in relation to HCC in West African population. HBX (complete or 3'-truncated) and HBS genes were assessed by PCR in cell-free DNA (CFDNA) from plasma of subjects recruited in a hospital-based case-control study (325 controls, 78 cirrhotic patients and 198 HCC cases) conducted in The Gambia. These samples had been previously analyzed for R249S and HBV serological status. Complete HBX sequence was frequently detected in CFDNA of HCC-R249S positive (77%, 43/56) compared with HCC-R249S-negative cases (44%, 22/50). Conversely, the proportion of 3'-truncated HBX gene was significantly higher in HCC-R249S negative than positive cases (34%, 17/50, compared with 12%, 7/56) (χ(2) = 12.12; P = 0.002; distribution of R249S negative and positive according to HBX status). Occult HBV infection (detected by PCR) was present in 24% of HCC previously considered as negative by HBV serology. Moreover, HBV mutation analysis revealed that double mutation at nucleotides 1762(T)/1764(A) was associated with diagnosis of cirrhosis or HCC {cirrhosis: odds ratio (OR): 9.50 [95% confidence interval (CI) 1.50-60.11]; HCC: OR: 11.29 [95% CI 2.07-61.47]}. These findings suggest that in HCC from The Gambia, complete HBX sequences are often associated with the presence of TP53 R249S mutation.

Successful treatment of hepatitis B virus associated nephrotic syndrome with oral Lamivudine in a Nigerian child: a case report.

Hepatitis B virus is a well described cause of nephrotic syndrome (NS) worldwide, the typical lesion being membranous glomerulonephropathy. HBV associated NS has been successfully treated with intravenous alpha interferon (IFN), an anti-viral agent. In recent times there have been reports of treatment with lamivudine, an orally administered nucleoside analogue inhibitor of HBV DNA polymerase in Caucasian children. Data is however limited and it's actual efficacy and safety in children is yet to be determined. We present the case of an 8-year-old Nigerian boy with NS and active hepatitis B virus infection. He went into remission 3 months after commencing oral lamivudine which he had for a year with no significant side effects observed. He remains in remission 3 years later. This, to our knowledge is the first report in literature of successful treatment in an African child.

New progress towards elimination of mother-to-child transmission of hepatitis B virus in China.

BACKGROUND: We conducted an evaluation on the potential data resources for the elimination of hepatitis B virus (HBV) mother-to-child transmission in China, so as to provide reference for WHO and other countries in the validation of HBV elimination of mother-to-child transmission (EMTCT) in a real-world large country setting. METHODS: We used the indicators set out in WHO Interim guidance for country validation of viral hepatitis elimination as the benchmark to evaluate the availability of data and progress against indicators for the elimination validation in China. We used descriptive analysis to illustrate the status of all indicators and parameters. RESULTS: According to the indicators which are recommended by WHO for HBV EMTCT validation, the national data in China are attainable, though not for HBV DNA testing for the HBsAg-positive mothers and their subsequent management. The remaining challenges for China are to consider how the national serosurvey might be conducted in future in the context of low HBV prevalence among children under 5 years; to collect systematically the programmatic impact data; to strengthen multi-sectoral collaboration among immunization, maternal and child health, hospital services, as well as other stakeholders. CONCLUSION: The available data on HBV EMTCT are sufficient to support the validation of the elimination of HBV mother-to-child transmission in China.

Worldwide prevalence of hepatitis B virus and hepatitis C virus among patients with cirrhosis at country, region, and global levels: a systematic review.

BACKGROUND: Empirical, updated country-level estimates on the proportion of cirrhosis attributable to viral hepatitis are required. We estimated the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection in patients with cirrhosis at country, regional, and global levels as an approximation for the fractions of cirrhosis attributable to viral hepatitis. METHODS: In this systematic review, we searched MEDLINE, Embase, Web of Science, and Scielo between Jan 1, 1993, and Aug 1, 2021. Studies were eligible if they reported on the prevalence of both HBV and HCV infection in representative studies of at least 20 patients with cirrhosis. Studies were excluded if they used first-generation HCV assays or were from a selected population of patients with cirrhosis (eg, patients selected based on specific causes, veterans, injecting drug users). Two authors (CJA and CdM) selected and extracted aggregated data from the selected publications. Data were extracted for study recruitment period, age, sex, and cause of cirrhosis, among others. Data about heavy alcohol consumption and non-alcoholic fatty liver disease (NAFLD) were also extracted when available. Aggregated data from studies from key publications were requested from the authors of the original study if selection of patients was unclear or information on causes was missing. We estimated the country-specific prevalence of causes of cirrhosis by pooling study-level data from the same country using a random-effects model. Subsequently, we estimated the regional (WHO region and UN subregion) and global prevalence by weighting the country-specific prevalence by the number of new liver cancer cases that occurred in 2020, as estimated in GLOBOCAN. The study was registered with PROSPERO, CRD42020149323. FINDINGS: Our database searches identified 21 338 records, and a further nine records were identified by scanning references of key publications. After excluding duplicates and assessing full-text articles for eligibility, 520 publications from 86 countries or territories (and reporting on 1 376 503 patients with cirrhosis) were included in the systematic review. The prevalence of HBV infection was lower among patients with cirrhosis in Europe, the Americas, and Oceania (UN subregional prevalence ranges 3-14%) than in Africa and Asia (8-61%). HCV infection prevalence was heterogenous, even within regions (12-83%). The combined prevalence of HBV and HCV infection exceeded 50% in most Asian and African regions. Globally, among patients with cirrhosis, 42% had HBV infection and 21% had HCV infection. The contribution of heavy alcohol use was highest in Europe (country range 16-78%), the Americas (17-52%), and Oceania (15-37%) and lowest in Asia (0-41%). Data on NAFLD were limited. INTERPRETATION: HBV and HCV could account for almost two thirds of the global burden of cirrhosis. With the availability of effective interventions for the prevention or treatment of HBV and HCV, the data presented in this study will help to effectively allocate resources towards viral hepatitis elimination and to design interventions at the country level. FUNDING: International Agency for Research on Cancer, World Health Organization.

Hepatocellular carcinoma: measures to improve the outlook in sub-Saharan Africa.

Hepatocellular carcinoma is a leading public health concern in sub-Saharan Africa, and it is most prevalent in young adults (median 45 years [IQR 35-57]). Overall, outcomes are poor, with a median survival of 2·5 months after presentation. Major risk factors for hepatocellular carcinoma are hepatitis B virus (HBV), hepatitis C virus, aflatoxin B1 exposure, and alcohol consumption, with metabolic dysfunction-associated fatty liver disease slowly emerging as a risk factor over the past few years. Crucially, these risk factors are preventable and manageable with effective implementation of the HBV birth-dose vaccination, treatment of chronic viral hepatitis, provision of harm reduction services, and by decreasing aflatoxin B1 exposure and harmful alcohol consumption. Primary prevention is central to the management of hepatocellular carcinoma, especially in poorly resourced environments. Effective screening and surveillance programmes with recall policies need to be implemented, because detection and curative management of hepatocellular carcinoma is possible if it is detected at an early stage, even in countries with minimal resources, with appropriate upskilling of medical personnel. The establishment of centres of excellence with advanced diagnostic and therapeutic capabilities within countries should improve hepatocellular carcinoma outcomes and assist in driving the implementation of much needed systematic data systems focused on hepatocellular carcinoma to establish the accurate burden in sub-Saharan Africa. Such data would support the public health importance of hepatocellular carcinoma and provide a strong basis for advocacy, programme development, resource allocation, and monitoring of progress in reducing mortality.

Aetiological differences in demographical, clinical and pathological characteristics of hepatocellular carcinoma in The Gambia.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide, with a high burden in West Africa. Data evaluating aetiological differences in HCC presentation from this region are limited. AIMS: The aim of this study was to describe the demographical, clinical and pathological characteristics of HCC by aetiology (hepatitis B or C infection, aflatoxin associated). METHODS: One hundred and ninty-three cases of HCC diagnosed between 1997 and 2001 in The Gambia were analysed. Characteristics were compared by aetiology using χ(2)-tests, student t-test and Wilcoxon's rank sum tests as appropriate. RESULTS: The prevalence of hepatitis B surface antigen, hepatitis C antibody and aflatoxin-associated 249(ser) TP53 mutations among HCC patients was 60, 20 and 38% respectively. The typical HCC patient was a 49-year-old male positive for hepatitis B surface antigen presenting with hepatomegaly (93%), abdominal pain (94%) and weight loss (95%) 8 weeks after symptom onset. Most patients had multifocal lesions with background cirrhosis. The median largest tumour was 10.3 cm and the median α-fetoprotein level was 500 ng/ml. Eighty-four per cent of patients had advanced HCC (patients not meeting the Milan criteria) at presentation. CONCLUSIONS: Irrespective of aetiological agent, HCC among West Africans presents at very advanced stages. Few clinical or pathological differences exist by aetiology. More studies are needed to understand the mechanisms of hepatocarcinogenesis among these patients as well as identify high-risk populations in which early detection through screening will be beneficial.

Health-care provision and policy for non-alcoholic fatty liver disease in sub-Saharan Africa.

Sub-Saharan Africa, which has a population of more than 1 billion people, carries 24% of the global burden of disease and spends the least on health care of any region, relying heavily on international development assistance to deliver health care for HIV, tuberculosis, and malaria. The demographic and epidemiological transitions occurring in sub-Saharan Africa, with rising prevalences of obesity and diabetes, enhance the risk of non-alcoholic fatty liver disease (NAFLD), yet this remains an unrecognised complication of metabolic syndrome. There are no guidance documents on NAFLD from sub-Saharan Africa, and non-communicable disease (NCD) guidance documents do not include the associated burden of fatty liver disease. Combating the health and socioeconomic burden of NAFLD requires an integrated liver health approach, with task-shifting to primary health care. Using clear guidance documents to link education and management of HIV, viral hepatitis, NAFLD, and associated NCDs is also crucial to an integrated approach to infectious diseases and NCDs, which requires targeted funding from both governments and international development agencies.

Upper Gastrointestinal Bleeding Secondary to an Incidental, Impacted Foreign Body in the Duodenum.

A 68-year-old woman presented with a three-week history of upper abdominal discomfort, vomiting of coffee ground substance, and passage of tarry stools. There were no typical risk factors for gastroduodenal or liver disease. Gastroscopy done showed a fishbone impacted in the wall of the pyloric opening with its free end abutting on the wall of the duodenum resulting in a duodenal ulcer. Antral erosions were also noted. Retrieval forceps were used to retrieve the fishbone. The patient did not remember eating any fish containing meal, and there was no odynophagia. This case emphasizes the importance of considering foreign bodies as a cause of upper gastrointestinal bleeding as well as the need for an endoscopic review of all patients with upper gastrointestinal bleed.

Hepatitis C viral load and genotypes among Nigerian subjects with chronic infection and implication for patient management: a retrospective review of data.

INTRODUCTION: Hepatitis C Virus (HCV) is highly infectious with no currently available vaccine. Prior to treatment, it is recommended to confirm HCV infection with either quantitative or qualitative nucleic acid test. Access to these assays in Nigeria is limited but for effective management of patients, HCV viral load (VL) prior to therapy is required and genotype may be needed in some instances. This study aimed at reviewing the pattern of HCV viral load and genotype in the country, and its implication in patient management. METHODS: this was a retrospective study that involved data abstraction from an electronic database of an accredited laboratory between June 2013 and May 2017. De-linked data were abstracted from records of adult subjects with HCV VL and genotype results, these were analysed using Microsoft Excel 2010 and SPSS v20. RESULTS: within the study period, 346 subjects had baseline VL and 134 (38.7%) had genotype results available. Of these, 202/346 (58.4%) had detectable VL results with higher prevalence in males (64.7%) and ≥51years (42.5%) age group. The median VL among 202 subjects was 407,430 (IQR: 96,388 - 1,357,012) IU/mL. Distribution of genotypes showed that genotypes 1 and 4 had prevalence of 63.2% and 16.8% respectively. CONCLUSION: genotypes 1 and 4 have the highest prevalence. A greater proportion of subjects had VL values ≤800,000 IU/mL, an indication that they are more likely to respond well to available antiviral therapy hence, access to these antivirals will greatly improve management of HCV infection in Nigeria.